Retinal degenerations are one of the major causes of irreversible blindness. This laboratory is pursuing several parallel projects with the goal of isolating genes that may be involved in retinal diseases. For this purpose, we have developed a solid-phase subtraction technique for isolating retina-/macula-specific genes. Using this technique, we have isolated several cDNAs that are exclusively or highly expressed in macula vs. peripheral retina. We have localized several of these macula-enriched genes to Best's, Bardet-Biedl's, and Starardt's loci. These genes are now being investigated as possible candidates in these diseases. Ultimately, we hope to build a sequence database of maculaenriched, chromosomally localized cDNAs that may serve as candidates for yet unlocalized macular diseases such as age-related macular degenerations. We have also cloned and sequenced the human phosphatidylinositol-specific phospholipase C beta-3 gene. This gene is located in 11q13 very close tot he PYGM locus, which links it to both Bardet-Biedl syndrome type I and Best's macular degeneration. We are investigating this gene as a possible candidate for these diseases.